MiR-139-5p regulates the Notch/RBP-J/Hes1 axis to promote homing of bone mesenchymal stem cells in bronchial asthma.
10.12122/j.issn.1673-4254.2024.12.03
- Author:
Kun WANG
1
;
Haoxiang FANG
1
;
Xiaomei CAO
1
;
Ziheng ZHU
2
Author Information
1. College of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230031, China.
2. Graduate School, Anhui University of Chinese Medicine, Hefei 230031, China.
- Publication Type:Journal Article
- Keywords:
Notch1 signaling pathway;
asthma;
bone mesenchymal stem cells;
miR-139-5p
- MeSH:
Asthma/genetics*;
Animals;
Mesenchymal Stem Cells/cytology*;
MicroRNAs/metabolism*;
Rats;
Transcription Factor HES-1/genetics*;
Signal Transduction;
Receptor, Notch1/genetics*;
Immunoglobulin J Recombination Signal Sequence-Binding Protein/genetics*;
Receptors, CXCR4/genetics*;
Coculture Techniques;
Rats, Sprague-Dawley;
Chemokine CXCL12/genetics*;
Epithelial Cells/metabolism*
- From:
Journal of Southern Medical University
2024;44(12):2283-2290
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To observe the role of miR-139-5p and Notch1 signaling pathway in regulation of homing of bone mesenchymal stem cells (BMSCs) of asthmatic rats.
METHODS:Normal rat BMSCs were co-cultured with bronchial epithelial cells from normal or asthmatic rats, followed by transfection with miR-139-5p mimics or a negative control sequence. The changes in cell viability and cell cycle were analyzed, and the cellular expressions of CXCR4 and SDF-1 were detected using immunofluorescence staining. The changes of BMSC homing after the transfection were observed, and the expressions of Notch1, RBP-J, and Hes1 mRNAs and proteins and Th1/Th2 cytokines were detected with RT-qPCR, Western blotting or ELISA.
RESULTS:The co-cultures of BMSCs and asthmatic bronchial epithelial cells showed significantly decreased expressions of miR-139-5p, IL-2 and IL-12 and increased expressions of CXCR4, SDF-1, IL-5, IL-9, Notch1, RBP-J, and Hes1. Transfection with miR-139-5p mimics significantly increased the expressions of miR-139-5p, IL-2, CXCR4 and SDF-1 and lowered the expression levels of IL-5, IL-9, Notch1, activated Notch1, and Hes1 in the co-cultured cells. Correlation analysis showed that BMSC homing was positively correlated with miR-139-5p and IL-12 and negatively correlated with IL-5 expression. The expression of CXCR4 was negatively correlated with activated Notch1, and SDF-1 was positively correlated with miR-139-5p but negatively correlated with Notch1 expression.
CONCLUSIONS:High expression of miR-139-5p promotes homing of BMSCs in asthma by targeting the Notch1 signaling pathway to regulate the expressions of Th1/Th2 cytokines, thereby alleviating airway inflammation.
